Cognitive Science 320

 

Glutamate and the different types of glutamate receptors

• The main excitatory transmitter in the CNS
• NMDA (N-methyl-D-aspartate) - type glutamate receptors
  • Are ionotropic with relatively large conductance and are activated by NMDA as well as glutamate.
  • These are directly-coupled, but the channel carries little current unless the membrane is depolarized.
  • At V_rest Mg⁺⁺ clogs the channel, but Mg⁺⁺ is pushed out by depolarization.
  • Once opened they are permeable to cations, including Ca⁺⁺ , K⁺, and Na⁺.
  • Once all the conditions are met the channels open and close very slowly.
  • APV (2 amino 5 phosphonovalerate) selectively blocks NMDA type glutamate receptors.
  • When activated these can trigger intracellular Ca⁺⁺ dependent second messenger system cascades.
    • Excessive influx of Ca⁺⁺ through NMDA receptors during repetitive stimulation has been implicated in neurotoxicity
    • Glutamate excitotoxicity
      • Probably due to increased I_Ca which leads to increased [Ca²⁺]_i
      • Cell damage after strokes, seizures and in some degenerative diseases may be caused by glutamate excitotoxicity
      • Agents that block the NMDA receptor may decrease the effects of glutamate excitotoxicity
  • These channels function only in the presence of glycine, glutamate and depolarization.
  • These receptors are inhibited by PCP (phencyclidine) which binds to a site within the open pore.
• Non-NMDA  types of glutamate receptors
  • These make up the predominant component of glutamate EPSPs in motor neurons activated by muscle sensory neurons.
  • Are ionotropic, directly-coupled fast-acting ion channels with relatively low permeability.
  • When activated they have increased permeability to Na⁺ and K⁺, most are not permeable to Ca⁺⁺
  • Some of these glutamate receptors are activated by AMPA (a-amino-3 hydroxy-5 methyl-4 isoxazole propionic acid)
  • Other glutamate receptors are activated by kainate or quisqualate
• Metabotropic glutamate receptors
  • Are linked to GTP-binding proteins and second messenger systems.
• Most cells which respond to glutamate have both NMDA and non-NMDA receptors